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T-wave morphology and atrio-ventricular conduction: insights from novel image-based models of the whole heart
[Thesis]. Manchester, UK: The University of Manchester; 2015.
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Abstract
Cardiovascular disease is a leading cause of death in developed countries, and places a huge demand on healthcare services and economies across the globe. In this thesis computational models of the rabbit and mouse whole heart were developed and used to investigate a variety of phenomena related to cardiac electrophysiology.In part I, a heterogeneous family of single cell models was developed for the rabbit ventricles. The models were incorporated into a 3D anatomical reconstruction, and subsequently used to study the relationship between ventricular heterogeneity and the electrocardiographic T-wave. It was found that, in order of significance, apico-basal, inter-ventricular and transmural heterogeneity had a lead-dependent effect on the T-wave of the 12-lead electrocardiogram. Subsequently, a detailed model of the rabbit whole heart was developed using image data from X-ray computed tomography, from which detailed anatomical structures were segmented and myocardial architecture determined. The developed 3D whole heart model exhibited physiological fibre structure and experimentally justified patterns of activation.In part II, a mathematical model of the mouse atrioventricular node was developed. The model was validated by its ability to show physiological pacemaking and response to ion channel blocking. The model was subsequently adapted to consider the heterogeneous nature of the atrioventricular node, and incorporated into a 2D simplistic tissue model of the whole heart. The developed model exhibited physiological atrioventricular conduction, and provided insights into the nature of dual-pathway electrophysiology and the role of the funny current. Finally, an optimisation study was carried out for contrast enhancement of X-ray computed tomography, specifically for imaging the mouse heart, the results of which may be used to facilitate future high-throughput imaging of cardiac tissue.